Effect of diindolylmethane on Ca2+ homeostasis and viability in PC3 human prostate cancer cells

Jeng Yu Tsai, Chiang Ting Chou, Shuih Inn Liu, Wei Zhe Liang, Chun Chi Kuo, Wei Chuan Liao, Ko Long Lin, Shu Shong Hsu, Yi Chau Lu, Jong Khing Huang, Chung Ren Jan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

12 Scopus citations


The effect of the natural product diindolylmethane on cytosolic Ca 2+ concentrations ([Ca2+]i) and viability in PC3 human prostate cancer cells was explored. The Ca2+-sensitive fluorescent dye fura-2 was applied to measure [Ca2+]i. Diindolylmethane at concentrations of 2050 M induced [Ca2+]i rise in a concentration-dependent manner. The response was reduced partly by removing Ca2+. Diindolylmethane-evoked Ca2+ entry was suppressed by nifedipine, econazole, SK&F96365, protein kinase C modulators and aristolochic acid. In the absence of extracellular Ca2+, incubation with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) inhibited or abolished diindolylmethane- induced [Ca2+]i rise. Incubation with diindolylmethane also inhibited thapsigargin or BHQ-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 reduced diindolylmethane-induced [Ca2+]i rise. At concentrations of 50100 M, diindolylmethane killed cells in a concentration-dependent manner. This cytotoxic effect was not altered by chelating cytosolic Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N, N′,N′-tetraacetic acid (BAPTA). Annexin V/PI staining data implicate that diindolylmethane (50 and 100 M) induced apoptosis in a concentration-dependent manner. In conclusion, diindolylmethane induced a [Ca2+]i rise in PC3 cells by evoking phospholipase C-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via phospholipase A2-sensitive store-operated Ca2+ channels. Diindolylmethane caused cell death in which apoptosis may participate.

Original languageEnglish
Pages (from-to)271-278
Number of pages8
JournalJournal of Receptors and Signal Transduction
Issue number5
StatePublished - 10 2012
Externally publishedYes


  • Ca
  • Diindolylmethane
  • PC3
  • Prostate


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